Paweł Górski

Publications of Paweł Górski

• The N363S and I559N single nucleotide polymorphisms of the h-GR/NR3C1 gene in patients with bronchial asthma.

  Authors: Michał Panek, Tadeusz Pietras, Adam Antczak, Artur Fabijan, Marcelina Przemęcka, Paweł Górski, Piotr Kuna, Janusz Szemraj

  International journal of molecular medicine. 04/2012;

  Bronchial asthma is a disease of multifactorial etiology. The natural variability of the DNA sequence within the h-GR/NR3C1 gene affects both the conformation and the activity of glucocorticoidBronchial asthma is a disease of multifactorial etiology. The natural variability of the DNA sequence within the h-GR/NR3C1 gene affects both the conformation and the activity of glucocorticoid receptors. There are 2 major types of resistance to glucocorticoids (GCS)-resistant asthma failing to respond to treatment with high doses of inhaled and oral glucocorticoids. Type I GCS-resistant asthma is cytokine-induced or acquired. Type II GCS resistance involves generalized primary cortisol resistance, which affects all tissues and is likely to be associated with a mutation in the glucocorticoid receptor (GCR) gene or in genes that modulate GCR function. There are clear examples of glucocorticoid gene h-GR/NR3C1 polymorphisms that can influence responses and sensitivity to glucocorticosteroids. Among the numerous polymorphisms observed within this gene, N363S and I559N single nucleotide polymorphisms (SNPs) may play an important role in the development of bronchial asthma and in the alteration of sensitivity to GCS in severe bronchial asthma. The aim of this research project was to study the correlation between the N363S and I559N polymorphisms of the h-GR/NR3C1 gene and the occurrence of asthma in a population of Polish asthmatics. Peripheral blood was obtained from 210 healthy volunteers and 234 asthma patients. Structuralized anamnesis, spirometry and allergy skin prick tests were performed in all participants. Genotyping was carried out using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and PCR-HRM methods. In the healthy, non-atopic population, the GG variant of the N363S polymorphism was found with a 5.7% frequency. In asthma patients, GG SNP of N363S occurred with the frequency of 6.4%. In the groups of patients with uncontrolled moderate asthma and uncontrolled severe disease, the genotype distribution for the investigated polymorphisms were as follows: N363S, AA, AG, GG occurring with 0.8750/0.0834/0.0416 frequency and I559N, TT, TA, AA occurring with 1.000/0.000/0.000 frequency. The analysis demonstrated a significantly higher frequency of the A and G variants of the N363S polymorphisms in uncontrolled moderate asthma and uncontrolled severe disease than in the healthy population. No variant-related differences in the frequency of the studied I559N polymorphism were demonstrated in healthy controls and asthma patients. In conclusion, the N363S polymorphism of the h-GR/NR3C1 gene is significantly associated with an increased sensitivity to glucococorticoids in vivo and susceptibility to the development of a moderate to severe form of uncontrolled bronchial asthma in the Polish population. This observation needs to be confirmed in a larger group of subjects.

• The role of functional single nucleotide polymorphisms of the human glucocorticoid receptor gene NR3C1 in Polish patients with bronchial asthma.

  Authors: Michał Panek, Tadeusz Pietras, Adam Antczak, Paweł Górski, Piotr Kuna, Janusz Szemraj

  Molecular biology reports. 04/2012; 39(4):4749-57.

  N363S and ER22/23EK polymorphisms observed within glucocorticoid receptor gene (NR3C1) may play an important role in the development of bronchial asthma. NR3C1 gene is associated with an alteredN363S and ER22/23EK polymorphisms observed within glucocorticoid receptor gene (NR3C1) may play an important role in the development of bronchial asthma. NR3C1 gene is associated with an altered sensitivity to GCs. The aim of the research project was to study the correlation between this NR3C1 gene polymorphisms and occurrence of asthma in the population of Polish asthmatics. Peripheral blood was obtained from 207 healthy volunteers and 221 asthma patients. Genotyping was carried out with PCR-RFLP method. In the groups of patients with uncontrolled moderate asthma and uncontrolled severe disease, the genotype distribution for the investigated polymorphisms was as follows: N363S-AA, AG, GG occurring with 0.881/0.073/0.046 frequency and ER22/23EK-GG, GA, AA occurring with 0.963/0.037/0.000 frequency. Chi-square analysis revealed a significantly different (P < 0.05) distribution between cases and controls for the N363S polymorphisms. The N363S polymorphism of NR3C1 gene is significantly associated with bronchial asthma, susceptibility to the development of moderate to severe form of uncontrolled bronchial asthma.

• [Intensity of depression in pedagogy students].

  Authors: Tadeusz Pietras, Andrzej Witusik, Michał Panek, Ewa Zielińska-Wyderkiewicz, Piotr Kuna, Paweł Górski

  Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 03/2012; 32(189):163-6.

  The teacher's profession is regarded to be susceptible to professional burnout. Its early markers include high neuroticism and tendency to depressive reactions. The aim of the study was to assess theThe teacher's profession is regarded to be susceptible to professional burnout. Its early markers include high neuroticism and tendency to depressive reactions. The aim of the study was to assess the depression intensity and the occurrence of mood disorders in the population of full-time and extramural course students of pedagogy aged 19-30, as well as the difference in intensity of the measured constructs between men and women. The study was carried out on the group of 223 women and 162 men aged 19-30 studying pedagogy at Piotrków Trybunalski Division of Jan Kochanowski Memorial University in Kielce in the years 2008-2011. The control group consisted of 76 women and 88 men studying economics. Students of full-time and extramural courses were included. All the participants were assessed with Beck Depression Inventory. Depression as a syndrome was diagnosed if the score of 10 of more was obtained. Among female students of pedagogy, 21 out of 223 obtained Beck Depression Inventory scores equal to, or above 10; whereas among female students of economics 1 out of 76 obtained such a result. The relative risk of developing depression (understood as Beck Depression Inventory result of 10 or more) was found to be significantly higher among female pedagogues (OR 7.797; CI 1.0306 to 58.9856) than among female economists. Among male pedagogy students, 2 out of 162 obtained 10 points, or more. It means that the risk of depression in female pedagogues was as much as over eight-fold higher than in male pedagogues (OR 8.3168; CI 1.9215 - 35.9979). The risk of depression in men studying pedagogy was not higher than in men studying economics, who obtained the Beck Depression Inventory scores of 10 or more in 1 case out of 88 (OR 1.1; CI 0.0983 to 12.3032). Considering all pedagogues irrespectively of gender versus all economists, the risk of depression in the group of pedagogues is over five-fold higher than among economists (OR 5.1464; CI 1.1991 to 22.0885). In the whole group of women, irrespectively of the study profile, the risk of Beck Depression Inventory result equal to, or exceeding was six-fold higher than among men (OR 6.5391; CI 1.9336 to 22.1144). There was no statistically significant correlation between the Beck Depression Inventory scores obtained in the studied group and the subjects' ages. The mean scores obtained in the particular groups are presented in table. The Beck Depression Inventory scores obtained by women studying pedagogy was found to differ with statistical significance from the scores obtained by male pedagogy students (p = 0.001925), female economics students (p = 0.015781) and female economics students (p = 0.000611). The mean intensity of depression in men studying pedagogy did not differ from the mean intensity of depression in women studying economics (p = 0.94128) and in men studying economics (p = 0.330382). No differences in the mean Beck Depression Inventory scores of female and male students of economics were noted, either (p = 0.444554). The mean intensity of depression in women representing both fields of study was 6.094 +/- 3.13, vs 4.97 +/- 2.45 in men; the difference was statistically significant at the significance level of p = 0.00005. The mean intensity of depression in pedagogy students of both sexes was 5.92 +/- 3.024 vs 4.79 +/- 2.39 in students of economics; the difference was statistically significant at the significance level of p = 0,000026. Women studying pedagogy demonstrate higher depression intensity than men studying pedagogy, as well as male and female students of economics. Students of pedagogy demonstrate higher depression intensity than students of economics. On the overall, women in the whole studied population have higher depression intensity than men; however, no such gender-related differences were observed among students of economics.

• Somatostatin receptor scintigraphy in sarcoidosis: relation to selected clinical and laboratory markers.

  Authors: Wojciech J Piotrowski, Małgorzata Bieńkiewicz, Izabella Frieske, Jerzy Marczak, Adam Antczak, Paweł Górski, Jacek Kuśmierek, Anna Płachcińska

  Polskie Archiwum Medycyny Wewnetrznej. 01/2012;

  INTRODUCTION: Differentiation between active and inactive sarcoidosis may be problematic. Several biochemical markers have been proposed for this purpose. Somatostatin receptor scintigraphy with theINTRODUCTION: Differentiation between active and inactive sarcoidosis may be problematic. Several biochemical markers have been proposed for this purpose. Somatostatin receptor scintigraphy with the use of 99mTc Tectreotide as a radiotracer may be used for estimation of disease activity. OBJECTIVES: To estimate the value of traditional biomarkers (serum angiotensin converting enzyme - SACE, C-reactive protein - CRP, markers of calcium metabolism, bronchoalveolar lavage fluid - BALF - lymphocytes) and a novel biomarker 8-isoprostane (8-IP) in exhaled breath condensate (EBC) for estimation of disease activity in relation to somatostatin receptor scintigraphy results. PATIENTS AND METHODS: 32 patients with sarcoidosis were included. 99mTc-HYNIC-TOC was used as a tracer, planar and SPECT/CT images were performed. Patients were divided into a subgroup with positive radiotracer uptake (n=20) and lack of visible uptake (n=12). 8-IP was measured in EBC by EIA method. RESULTS: We found a significant difference between the positive and negative uptake group in EBC 8-IP (19.119.8 vs 5.43.5 pg/ml, p=0.02). The concentration of SACE and % of BALF lymphocytes were also elevated, but did not reach the statistical significance. In the group of patients with positive scintigraphy results, a positive correlation was found between the uptake ratio and SACE (r=0.44, p=0.041). We show examples of practical application of somatostatin receptor scintigraphy for estimation of disease activity. CONCLUSIONS: The study shows low value of biochemical markers in clinical monitoring of sarcoidosis, but indicates the potential usefulness of somatostatin receptor scintigraphy in the monitoring of sarcoidosis.

• Asthma control, quality of life and successful sputum induction.

  Authors: Sebastian Majewski, Piotr Cichocki, Małgorzata Stępnicka-Bindemann, Paweł Górski

  Archives of medical science : AMS. 10/2011; 7(5):840-3.

  Induced sputum is widely used in clinical practice and scientific studies. This technique has become enormously useful in assessment of airway inflammation. However, some asthmatics are unable toInduced sputum is widely used in clinical practice and scientific studies. This technique has become enormously useful in assessment of airway inflammation. However, some asthmatics are unable to expectorate sputum of sufficient quality and quantity necessary for further processing, therefore not providing reliable results. This research study aimed to examine whether asthma control and asthma quality of life influence the results of sputum induction. Fourty-seven adult subjects, current non-smokers with symptomatic asthma, were studied. All participants underwent clinical assessment, skin prick testing, spirometry and sputum induction. Before sputum induction, subjects were asked to fill in the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) and Asthma Control Questionnaire (ACQ). Twenty-nine (62%) subjects produced sputum eligible for processing. This group had a significantly lower ACQ score (0.83 ±0.65 vs. 1.37 ±0.77; p = 0.02), higher MiniAQLQ total score (5.67 ±0.99 vs. 4.86 ±1.07; p = 0.011), higher MiniAQLQ symptoms domain score (5.54 ±1.13 vs. 4.63 ±1.24; p = 0.013) and higher MiniAQLQ activity limitations domain score (6.08 ±0.92 vs. 5.07 ±1.37; p= 0.014). The noted differences between groups of patients were not only statistically but were clinically important. The study results suggest that successful sputum induction may be expected in patients with better asthma control and better quality of life.

• The selected genetic polymorphisms of metalloproteinases MMP2, 7, 9 and MMP inhibitor TIMP2 in sarcoidosis.

  Authors: Wojciech J Piotrowski, Paweł Górski, Tadeusz Pietras, Wojciech Fendler, Janusz Szemraj

  Medical science monitor : international medical journal of experimental and clinical research. 10/2011; 17(10):CR598-607.

  Increased activity of metalloproteinases may play a role in the initiation and propagation of inflammation in sarcoidosis, and may also be one of the factors responsible for the development of lungIncreased activity of metalloproteinases may play a role in the initiation and propagation of inflammation in sarcoidosis, and may also be one of the factors responsible for the development of lung fibrosis. The aim of this study was to verify whether polymorphisms of MMP2 C-735T, MMP7 A-181G, MMP9 T-1702A and tissue inhibitor of metalloproteinase (TIMP)2 G-418C predispose to sarcoidosis. The study included 139 patients with sarcoidosis and 100 healthy subjects. MMPs and TIMP2 mRNA were measured in peripheral blood lysate using real-time RT-PCR. DNA for genetic polymorphism was extracted from peripheral blood by GTC method. Protein concentrations in peripheral blood lysates were measured by ELISA, and MMP2 and 9 activities in BAL fluid were estimated by gel zymography. TT genotype in MMP9 T-1702A was more frequent in sarcoidosis (p<0.0001, OR = 13.71, 95% CI 7.02-26.80) and resulted in higher expression of MMP9 mRNA (p<0.0001). No differences were found between TT and AT/AA patients in terms of radiological stage, lung function test parameters, activity markers and the presence/absence of Löfgren syndrome. There were no differences in the distribution of MMP2, MMP7 and TIMP2 polymorphisms. Messenger RNAs, as well as protein concentrations of MMP2, 7, 9, and TIMP2 were elevated in patients with sarcoidosis (p<0.0001 for each). The TT homozygotes of MMP9 T-1702A genotype may be predisposed to sarcoidosis. Elevated MMP2, 7, 9, and TIMP2 mRNAs suggest their inducibility.

• Functional polymorphism of cyclooxygenase-2 gene (G-765C) in chronic obstructive pulmonary disease patients.

  Authors: Tadeusz Pietras, Janusz Szemraj, Michał Panek, Andrzej Witusik, Maciej Banasiak, Adam Antczak, Paweł Górski

  Molecular biology reports. 06/2011; 39(3):2163-7.

  Cyclooxygenase two (COX-2) is an important enzyme metabolizing arachidonic acid. In contrast to constitutive cyclooxygenase one (COX-1), COX-2 is induced by proinflammatory factors. Polymorphism -765Cyclooxygenase two (COX-2) is an important enzyme metabolizing arachidonic acid. In contrast to constitutive cyclooxygenase one (COX-1), COX-2 is induced by proinflammatory factors. Polymorphism -765 G/C in COX-2-encoding gene promoter is associated with development of Alzheimer's disease, depression, carcinoma of the pancreas in smokers, breast cancer and rheumatoid arthritis. It is interesting whether the -765 G/C polymorphism in COX-2-encoding gene promoter can be associated with COPD, a disease which is inflammatory in character. It is highly probable as the breast and pancreas cancers, whose associations with the analyzed polymorphism have been studied, are smoking-dependent tumors. Additionally, tobacco smoke has been demonstrated to induce COX-2 in the lungs. The study group consisted of 122 COPD patients (48 females, 74 males). The control group consisted of 149 healthy nonsmoking subjects (83 females, 66 males). Polymerase chain reaction/restriction fragment length polymorphism was used for genotyping. A statistically significant difference in genotype distribution was observed as a result of the comparison between healthy subjects and patients with COPD. The distribution of alleles in both groups conformed with Hardy-Weinberg equilibrium. In the group of COPD patients, GG allele was found in 79 subjects, GC in 36, and CC in 7 subjects (F = 0.094, P = 0.296927); in the control group, 73 subjects had GG allele, 68--GC and 8--CC (F = 0.12728, P = 0.120265). The allele frequency revealed differences between those groups, attaining the level of statistical significance (χ(2) = 29.043, df = 2, P = 0.0000. The carriers of -765 G allele are at 1.53-fold higher risk of developing COPD. The presence of GG genotype does not increase significantly the risk of the disease. It is also noteworthy that the carriers of CC or GC genotypes are at significantly lower risk of developing COPD than the group of subjects with GG genotype.

• Anxiety, depression and methods of stress coping in patients with nicotine dependence syndrome.

  Authors: Tadeusz Pietras, Andrzej Witusik, Michał Panek, Janusz Szemraj, Paweł Górski

  Medical science monitor : international medical journal of experimental and clinical research. 05/2011; 17(5):CR272-6.

  Nicotinism is the most common addiction in Poland. Nicotine dependence is the cause of numerous behavioral diseases, including ischemic heart disease, neoplasms and chronic obstructive pulmonaryNicotinism is the most common addiction in Poland. Nicotine dependence is the cause of numerous behavioral diseases, including ischemic heart disease, neoplasms and chronic obstructive pulmonary disease. A question arises whether a tendency to anxiety and depressive reactions, as well as the strategies of coping with stressful situations, is involved in the clinical presentation of this addiction. The study was conducted in a group of 88 nicotine addicts without serious systemic comorbidities and in 84 healthy subjects. All the participants were assessed with Beck Depression Inventory (BDI), Spielberger State-Trait Anxiety Inventory (STAI) and the Coping Inventory for Stressful Situations (CISS). The mean intensity of anxiety as a trait and anxiety as a state, as well as its level, were found to differ between the groups (Sten 6.28±1.52 and 4.86±1.05, p=0,0000 for the trait, and 6.09±1.25 and 4.92±1.29, p=0.0000, for the state, respectively). Similarly, depression was demonstrated to be more intensive in nicotine addicts than in healthy subjects (12.76 points ±4.77 vs. 10.76±4.83, p=0.007). Among the 5 scales assessed by CISS, smokers demonstrated higher prevalence of emotion-oriented coping than controls (standard 9 6.27±1.70 in smokers vs. 5.67±1.57, p=0.019) and involvement in distracting activities (5.84±1.48 vs. 5.28±1.46, p=0.014). The obtained results indicate that anxiety and depression, as well as differences in coping with stress situations, distinguish nicotine addicts from non-smokers.

• Intravenous immunoglobulin replacement therapy in the treatment of patients with common variable immunodeficiency disease: an open-label prospective study.

  Authors: Karolina Kasztalska, Maciej Ciebiada, Barbara Cebula-Obrzut, Paweł Górski

  Clinical drug investigation. 01/2011; 31(5):299-307.

  Common variable immunodeficiency (CVID) is characterized by humoral immunodeficiency resulting in increased susceptibility to infections and diminished responses to protein and polysaccharideCommon variable immunodeficiency (CVID) is characterized by humoral immunodeficiency resulting in increased susceptibility to infections and diminished responses to protein and polysaccharide vaccines. Intravenous immunoglobulins (IVIgs) constitute a replacement therapeutic regimen for CVID and other primary and selected secondary immunodeficiencies but their mode of action is still not fully understood. The purpose of this study was to assess the effect of IVIg replacement therapy on the population of regulatory T cells (cells expressing CD4, CD25 and low levels of CD127) [T(regs)]), plasma levels of interleukin (IL)-2 and IL-10, and expression of fragment, crystallizable γ receptor IIb (Fc γ RIIb) [CD32b] on CD19+ B cells in CVID patients. This was an open-label prospective trial that included 17 CVID patients and seven healthy subjects as case controls. The diagnosis of CVID was primarily established by clinical criteria designed by the European Society for Immunodeficiencies (ESID) and was confirmed by low serum levels of two out of three subclasses of immunoglobulins (IgG, IgA or IgM). All CVID patients were treated with the IVIg preparation Flebogamma® 5%, a highly purified, pasteurized normal human IgG extracted from the serum of healthy individuals, administered at a dose of 300 mg/kg by slow 2-hour intravenous infusion. Blood samples were collected 30 minutes before the infusion and 30 minutes and 2 weeks after the termination of the infusion. We examined: (i) the plasma levels of IL-2 and IL-10; (ii) the percentage of CD4+ T cells and T(regs); and (iii) the expression of Fc γ RIIb on the surface of CD19+ B cells. CVID patients had higher plasma levels of IL-2 (p = 0.045) and IL-10 (p = 0.002) as well as a higher expression of Fc γ RIIb on CD19+ B cells (p =  0.0119) before IVIg compared with healthy controls. The infusion of IVIg led to further increases in the plasma levels of these cytokines 30 minutes after the termination of the infusion versus baseline (IL-2: p =  0.0004; IL-10: p = 0.0003). IVIg did not affect the expression of Fc γ RIIb. Finally, IVIg infusion resulted in elevation of the percentages of CD4+ T cells (p = 0.028) and T(regs) (p = 0.006) in the blood 30 minutes after the infusion. Flebogamma® 5% as replacement therapy not only supplies immunoglobulins but also modulates the immune response, and in this way may provide additional benefits to patients with CVID.

• Exhaled 8-isoprostane in sarcoidosis: relation to superoxide anion production by bronchoalveolar lavage cells.

  Authors: Wojciech J Piotrowski, Zofia Kurmanowska, Adam Antczak, Jerzy Marczak, Maciej Ciebiada, Paweł Górski

  Inflammation research : official journal of the European Histamine Research Society ... [et al.]. 12/2010; 59(12):1027-32.

  This study was designed to examine the mutual relationship between 8-isoprostane in exhaled breath condensate (EBC) and superoxide anion generation by bronchoalveolar lavage fluid (BALF) cells inThis study was designed to examine the mutual relationship between 8-isoprostane in exhaled breath condensate (EBC) and superoxide anion generation by bronchoalveolar lavage fluid (BALF) cells in patients with sarcoidosis. About 29 patients with sarcoidosis, 34 healthy never smokers (control group for EBC) and 15 healthy never smokers (control group for BAL) were examined. EBC was collected directly before bronchoscopy. 8-Isoprostane was measured by ELISA, and superoxide anion by colorimetry. Exhaled breath condensate 8-isoprostane is increased in sarcoidosis (median, 25-75 percentile): 2.50; 2.50-3.90 versus 6.20; 2.50-16.95 pg/ml, p ≤ 0.05). Spontaneous superoxide anion release from BALF cells was significantly elevated only in patients with a high percentage of lymphocytes in BALF (6.42 ± 1.24 vs. 23.52 ± 4.30 nmol/10(6) cells, p ≤ 0.01). There were no correlations between 8-isoprostane and spontaneous or stimulated superoxide anion release. We confirmed higher concentrations of EBC 8-isoprostane in sarcoidosis and higher spontaneous release of superoxide anion from BALF cells in patients with sarcoidosis. The increase of EBC 8-isoprostane is not directly related to superoxide anion released from BALF cells.

• The Bcl I single nucleotide polymorphism of the human glucocorticoid receptor gene h-GR/NR3C1 promoter in patients with bronchial asthma: pilot study.

  Authors: Tadeusz Pietras, Michał Panek, Damian Tworek, Katarzyna Oszajca, Radosław Wujcik, Paweł Górski, Piotr Kuna, Janusz Szemraj

  Molecular biology reports. 11/2010; 38(6):3953-8.

  Bcl I in the promoter polymorphism observed within h-GR/NR3C1 gene may play an important role in the development of bronchial asthma and resistance to GCs in the severe bronchial asthma. The aim ofBcl I in the promoter polymorphism observed within h-GR/NR3C1 gene may play an important role in the development of bronchial asthma and resistance to GCs in the severe bronchial asthma. The aim of the investigation was to study the correlation between this h-GR/NR3C1 gene polymorphism and occurrence of asthma in the population of Polish asthmatics. Peripheral blood was obtained from 70 healthy volunteers and 59 asthma patients. Structuralized anamnesis, spirometry and allergy skin prick tests were performed in all participants. Genotyping was carried out with PCR-RFLP method. In healthy, non-atopic population variants of Bcl I: GG, GC, CC were found with frequency 0.129/0.471/0.400, respectively. In asthma patients Bcl I: GG, GC, CC occurred with respective frequencies of 0.410/0.462/0.128. Chi-square analysis revealed a significantly different (P<0.05) distribution between cases and controls for the Bcl I polymorphism. The Bcl I polymorphism of h-GR/NR3C1 gene is significantly associated with bronchial asthma, susceptibility to the development of severe form and resistance to GCs in Polish population.

• [Mechanism of action of immunoglobulin applied intravenously].

  Authors: Karolina Kasztalska, Maciej Ciebiada, Paweł Górski

  Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 10/2010; 29(172):263-8.

  Intravenously applied immunoglobulin (IVIg) are used in medicine over 50 years. Beneficial effects of IVIg therapy have been described in the treatment of primary immunodeficiencies, inflammatory andIntravenously applied immunoglobulin (IVIg) are used in medicine over 50 years. Beneficial effects of IVIg therapy have been described in the treatment of primary immunodeficiencies, inflammatory and autoimmune diseases, and new applications are still searched. Nevertheless, the mechanisms responsible for the therapeutic effectiveness of antibodies have not been exactly known. The efficacy of IVIg preparates used in therapeutic doses in infectious and autoimmune diseases indicates on the anti-inflammatory activity resulting from the inhibition of immune cells via different ways. These mechanisms include blocking Fc gamma receptors, modulation of cytokines synthesis and secretion and modulation of antigens on surface of immunocompetent cells. By contrast, IVIg therapy used in the replacement dose gives quite the opposite effect. Substitutive immunoglobulins not only complement the deficiency of antibodies in primary and secondary immunodeficiencies but also have the immunomodulatory and even proinflammatory effect.

• The sequence polymorphism of MnSOD gene in subjects with respiratory insufficiency in COPD.

  Authors: Tadeusz Pietras, Janusz Szemraj, Andrzej Witusik, Monika Hołub, Michał Panek, Radosław Wujcik, Paweł Górski

  Medical science monitor : international medical journal of experimental and clinical research. 09/2010; 16(9):CR427-32.

  Chronic obstructive pulmonary disease (COPD) is associated with the development of respiratory failure, which, in turn, exposes the tissues to oxidative stress, which is both a cause and a result ofChronic obstructive pulmonary disease (COPD) is associated with the development of respiratory failure, which, in turn, exposes the tissues to oxidative stress, which is both a cause and a result of respiratory insufficiency. The first-line defense against oxidative stress is provided by the mitochondrial enzyme manganese superoxide dismutase (MnSOD), which is a superoxide anion scavenger. It is unknown whether genetic variability of the enzymes protecting against reactive oxygen species (ROS) can influence the development of respiratory failure in COPD patients. The aim of the study was to determine the correlation between polymorphism of MnSOD signal peptide and the occurrence of respiratory failure in the course of COPD. The study group consisted of 162 COPD patients (113 men and 49 women). The control group consisted of 63 subjects. Respiratory failure was diagnosed in 42 COPD patients. In all the examined subjects, the polymorphism resulting in alanine at residue 9 being replaced by valine and the expression of MnSOD in blood cells were determined. The Val/Val phenotype was demonstrated to occur in COPD patients more frequently than in the control group, as well as being associated with a lower expression level of MnSOD mRNA. Respiratory failure in the course of COPD also correlates with lower expression of MnSOD mRNA. The presence of valine at position 9 of the MnSOD signal peptide encoded by exon 2 is a risk factor for the occurrence of respiratory failure in the course of COPD in the Polish population.

• [Anxiety, depression and polymorphism of the gene encoding superoxide dismutase in patients with chronic obstructive pulmonary disease].

  Authors: Tadeusz Pietras, Andrzej Witusik, Michał Panek, Piotr Gałecki, Janusz Szemraj, Paweł Górski

  Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 09/2010; 29(171):165-8.

  Chronic obstructive pulmonary disease (COPD) is a severe systemic disease leading to circulatory and respiratory failure. COPD is also a risk factor for the onset of anxiety and mood disturbances.Chronic obstructive pulmonary disease (COPD) is a severe systemic disease leading to circulatory and respiratory failure. COPD is also a risk factor for the onset of anxiety and mood disturbances. Identification of the correlates of emotional disturbances in the course of COPD can make it possible, on the one hand, to prevent mental and behavioral disorders early in the course of this serious somatic disease, and on the other hand, to institute appropriate treatment. The aim of the study was to determine the correlation between the polymorphism of manganese superoxide dismutase signal peptide and the severity of anxiety and depression in COPD patients. The study group consisted of 57 patients with grade I, II and III COPD according to GOLD criteria. The control group consisted of 63 healthy nicotine addicts. In all the subjects, the genotype of position 9 of manganese superoxide dismutase signal peptide was determined, depression severity was measured with Beck Depression Scale, and anxiety as a trait and as a state was measured with Spielberg State/Trait Anxiety Inventory (STAI). Among COPT patients, 16 subjects were found to have Ala/Ala genotype, 23 Val/Ala and 18 Val/Val. In the smokers' group Ala/Ala genotype was found in 29 cases, Val/Ala in 27 and Val/Val in 7. The distribution of genotype frequencies differed between the groups. In COPD patients, the mean depression severity assessed according to Beck Scale amounted to (16.52 +/- 5.63) and was higher than in smokers without COPD (13.85 +/- 4.24, p = 0.003828). The average severity of anxiety as a trait and as a state did not differ significantly in both groups. Among COPD patients, the mean severity of depressive disorders in subjects with Val/ Val genotype was 21.27 +/- 4.32 and was significantly higher than in those with Val/Ala (15.22 +/- 5.29) and Ala/Ala (12.87 +/- 3.72) genotypes. The severity of anxiety as a trait in COPD patients reached 7.72 +/- 1.21 in the subgroup with Val/Val genotype and was also higher than in those with Val/Ala genotype (6.69 +/- 1.48) and with Ala/Ala genotype (5.87 +/- 1.14). A similar correlation was observed for anxiety as a state (subjects with Val/Val genotype 6.78 +/- 1.06, with Val/Ala genotype 6.18 +/- 1.01 and with Ala/ Ala genotype 5.88 +/- 1.41). Among healthy smokers, the mean severities of depression, anxiety as a trait and anxiety as a state did not differ in subjects with different genotypes. The study has demonstrated that the severity of depression is higher in COPD patients than in the group of healthy smokers. In the group of patients with COPD, Val/Val genotype at position 9 of MnSOD signal peptide is associated with more severe depression, anxiety as a trait and anxiety as a state in comparison with patients who have Val/Ala and Ala/Ala genotypes. No similar correlations were found in healthy smokers.

• Rhinosinusitis in COPD: symptoms, mucosal changes, nasal lavage cells and eicosanoids.

  Authors: Violetta M Piotrowska, Wojciech J Piotrowski, Zofia Kurmanowska, Jerzy Marczak, Paweł Górski, Adam Antczak

  International journal of chronic obstructive pulmonary disease. 01/2010; 5:107-17.

  The coexistence of upper airways disease with chronic obstructive pulmonary disease (COPD) is not well documented. The aim of this research was to assess sino-nasal inflammation in COPD by variousThe coexistence of upper airways disease with chronic obstructive pulmonary disease (COPD) is not well documented. The aim of this research was to assess sino-nasal inflammation in COPD by various tools, and look for the impact on quality of life, relation to smoking, disease severity and systemic inflammation. Current and ex-smokers with COPD (n = 42) and healthy never-smokers (n = 21) were included in this study. COPD severity was assessed by GOLD criteria and BODE index. Markers of systemic inflammation were measured. Nasal symptoms and general quality of life were assessed using the questionnaires; sino-nasal questionnaire (SNAQ-11) and St. George's Respiratory Questionnaire (SGRQ). Nasal endoscopy and saccharine test were performed. Nasal lavages were collected for cytological examination and eicosanoids (cysteinyl leukotrienes, leukotriene B4, 8-isoprostane). Symptoms and endoscopic scores were higher in COPD (P < or = 0.0001). Only SGRQ symptoms subscore correlated with SNAQ-11 (r = 0.34, P = 0.035). Mucociliary clearance was impaired only in current smokers (9.91 +/- 0.49 versus 13.12 +/- 0.68 minutes, P < or = 0.001). 8-isoprostane was higher in COPD smokers compared to the controls (0.17 +/- 0.04 versus 0.34 +/- 0.09 pg/g protein, P < 0.05). Endoscopic score and mucociliary of impairment patients who currently smoked cigarettes correlated with concentrations of 8-isoprostane. None of the parameters correlated with disease severity and markers of systemic inflammation. We provide evidence of upper airways disease in COPD, which appears to be related more to patients who currently smoke than to disease severity.

• [The analysis of the factors influencing the development of glucocorticoid resistance in the etiopathogenesis of severe bronchial asthma].

  Authors: Michał Panek, Tadeusz Pietras, Izabela Kupryś-Lipińska, Paweł Górski, Piotr Kuna, Janusz Szemraj

  Postepy biochemii. 01/2010; 56(4):373-82.

  Bronchial asthma is a disease of multi - factored etiology. Current data show that multiple genes may be involved in the pathogenesis of asthma. Corticosteroids (GCS) are the most effectiveBronchial asthma is a disease of multi - factored etiology. Current data show that multiple genes may be involved in the pathogenesis of asthma. Corticosteroids (GCS) are the most effective anti-inflammatory therapy for inflammatory disease such as bronchial asthma. There are 2 major types of GCS-resistant asthma to treatment of high doses of inhaled and oral glucocorticoids. Type I GCS-resistant asthma is cytokine-induced or acquired. Type II GCS resistance involves generalized primary cortisol resistance, which affects all tissues and is likely associated with a mutation in the GCR gene or in genes that modulate GCR function. There are clear examples of glucocorticoid gene h-GCR/NR3C1 polymorphisms that can influence responses and sensitivity to glucocorticosteroids. This article may lead to holistic the development analysis of the factors determining the progress of the glucocorticoid resistance in the severe bronchial asthma with special acknowledgement of the influence of polymorphisms of the glucocorticoid receptor gene h-GCR/NR3C1 to formation GCS resistance.

• Exhaled 8-isoprostane as a prognostic marker in sarcoidosis. A short term follow-up.

  Authors: Wojciech J Piotrowski, Zofia Kurmanowska, Adam Antczak, Jerzy Marczak, Paweł Górski

  BMC pulmonary medicine. 01/2010; 10:23.

  8-Isoprostane (8-IP) is a marker of lipid peroxidation. Elevated concentrations have been reported in BAL fluid and exhaled breath condensate (EBC) in sarcoidosis (S). To validate the prognostic8-Isoprostane (8-IP) is a marker of lipid peroxidation. Elevated concentrations have been reported in BAL fluid and exhaled breath condensate (EBC) in sarcoidosis (S). To validate the prognostic value of this marker we tested whether: 1. high initial EBC 8-IP predispose to more severe disease; 2. low initial concentrations increase a chance of early remission; 3. remissions are connected with the decrease of EBC 8-IP. 40 patients (S) have been examined initially (V1) and after 8.5 +/- 0.5 months (V2). EBC 8-IP concentrations were measured by ELISA. Chest X-ray, lung function test, serum ACE and Ca2+ concentrations, 24 hrs Ca2+loss, abdominal ultrasonography, symptoms evaluation were performed. We confirmed higher concentrations of 8-IP in EBC of patients with sarcoidosis (p = 0.001). Relative risk (RR) of persistence of disease at V2 when initial 8-IP was above 20 pg/mL was 1.04, and the frequency distributions estimated by chi2 test were not significantly different. A chance (RR) of early complete remission when V1 8-IP was below DL, was 3.33 (p = 0.04 by chi2 test). A significant decrease of 8-IP at V2 was observed only in patients who received treatment (p = 0.03), but not in those with spontaneous remission. We come to the conclusion, that low initial 8-IP may be a positive prognostic factor. A decrease of 8-IP in treated patients reflects a non-specific effect of treatment and is not related to mere regression of disease.

• Hepatocyte growth factor in exhaled breath and BAL fluid in sarcoidosis.

  Authors: Wojciech J Piotrowski, Zofia Kurmanowska, Adam Antczak, Jerzy Marczak, Paweł Górski

  Pneumonologia i alergologia polska : organ Polskiego Towarzystwa Ftyzjopneumonologicznego, Polskiego Towarzystwa Alergologicznego, i Instytutu Gruźlicy i Chorób Płuc. 01/2010; 78(3):187-91.

  Hepatocyte growth factor (HGF) is a strong mitogen stimulating lung epithelial cell growth. Elevated levels of HGF have been reported in various biological materials of patients with acuteHepatocyte growth factor (HGF) is a strong mitogen stimulating lung epithelial cell growth. Elevated levels of HGF have been reported in various biological materials of patients with acute respiratory distress syndrome and in patients recovering from pneumonia or pneumonectomy. Sarcoidosis may be complicated by lung fibrosis. Consequently, HGF could be considered a new biomarker identifying patients with a higher risk of lung fibrosis. The aim of the study was to verify whether: 1. HGF is measurable in bronchoalveolar lavage fluid (BALF) and exhaled breath condensate (EBC); 2. HGF in BALF or EBC is impaired in sarcoidosis; and 3. HGF correlates with chosen activity and prognostic markers. Sixty-four EBC and 30 BALF of sarcoid patients, and 15 and 9 of healthy controls, respectively, were collected for the measurement of HGF using an ELISA test. HGF was detectable in 62% of EBC samples (56% sarcoidosis and 87% of controls) and in all the BALF samples. EBC and BALF concentrations were not different in comparison to the controls. Moreover, no correlation was found between EBC/BALF concentrations and radiological stage, lung function tests, duration of disease, number of relapses, BALF lymphocytes, serum ACE, or serum and urine calcium concentrations. HGF is detectable in BAL and EBC. However, it does not distinguish sarcoidosis patients from healthy subjects. The above, as well as the lack of correlations with various parameters of disease activity and severity rule out EBC/ /BALF HGF as a biomarker for sarcoidosis monitoring.

• Superoxide anion production by bronchoalveolar lavage cells in relation to cellular composition and lung function in sarcoidosis and chronic bronchitis.

  Authors: Wojciech J Piotrowski, Zofia Kurmanowska, Adam Antczak, Jerzy Marczak, Sebastian Majewski, Paweł Górski

  Polskie archiwum medycyny wewnȩtrznej. 12/2009; 119(12):777-84.

  INTRODUCTION: Increased generation of superoxide anion (O2 -.) by bronchoalveolar lavage (BAL) cells has been reported in various inflammatory disorders. However, the clinical relevance of thisINTRODUCTION: Increased generation of superoxide anion (O2 -.) by bronchoalveolar lavage (BAL) cells has been reported in various inflammatory disorders. However, the clinical relevance of this phenomenon is unclear. OBJECTIVES: The aim of the study was to investigate whether production of O2-. is enhanced in smoking-related chronic bronchitis and sarcoidosis, and to assess a relationship between O2-. generation and lung function impairment and changes in BAL cellular pattern. PATIENTS AND METHODS: Forty-two patients with sarcoidosis, 24 smokers with chronic bronchitis, and 17 controls were examined. A number/percentage of BAL cells was calculated. Spontaneous and phorbol myristate acetate (PMA)-stimulated O2-. production was measured in BAL cells. Spirometry was performed. RESULTS: Patients with smoking-related chronic bronchitis produced more O2 -. spontaneously (6.42 -/+1.24 vs. 15.39 -/+2.47 nmol/106 cells, P = 0.003) and after stimulation (3.73 -/+1.32 vs. 14.76 -/+2.79 nmol/106 cells; P = 0.001). PMA-stimulated excess production correlated with the percentage of neutrophils (r = 0.66, P = 0.0005). In sarcoidosis, only spontaneous production of O2 -. was higher (vs. 18.07 -/+2.49 nmol/106 cells, P = 0.004) and correlated with the percentage of BAL lymphocytes. There was no correlation between O2-. production and lung function parameters. CONCLUSIONS: Patients with smoking-related chronic bronchitis produce more O2-., and this phenomenon is related to BAL neutrophils. In sarcoidosis, spontaneous release of O2-. from BAL cells is related to the extent of lymphocytic alveolitis. Higher O2-. generation did not impair lung function.

• Metalloproteinases MMP-9, MMP-2 and their tissue inhibitors TIMP-1, TIMP-2 in peripheral transbronchial lung biopsies of patients with sarcoidosis.

  Authors: Wojciech J Piotrowski, Agnieszka Nawrocka-Kunecka, Adam Antczak, Jerzy Marczak, Romuald Biernacki, Piotr Kordek, Zofia Kurmanowska, Paweł Górski

  Polskie archiwum medycyny wewnȩtrznej. 10/2009; 119(10):628-35.

  INTRODUCTION: The imbalance between metalloproteinases (MMPs) and their tissue inhibitors TIMPs) may be involved in the pathogenesis of lung sarcoidosis, a granulomatous inflammatory disease whichINTRODUCTION: The imbalance between metalloproteinases (MMPs) and their tissue inhibitors TIMPs) may be involved in the pathogenesis of lung sarcoidosis, a granulomatous inflammatory disease which may lead to lung fibrosis. OBJECTIVES: The aim of the study was to verify whether the expression of MMP-9, MMP-2, TIMP-1, and TIMP-2 in peripheral lung biopsies of patients with sarcoidosis correlate with lung function tests, radiological pattern, and bronchoalveolar lavage (BAL) cells. We compared the expression of MMPs and TIMPs between patients with sarcoid-positive vs. - negative biopsy and fibrosing vs. non-fibrosing high-resolution computed tomography (HRCT)pattern. PATIENTS AND METHODS: We examined patients with histologically proven stage II and III sarcoidosis (n = 17). Immunohistochemistry with antibodies against the studied molecules was performed in the lung and bronchial tissue specimens obtained from transbronchial lung biopsies. The radiological pattern was evaluated based on HRCT. The total cell number and percentage of cells were calculated in the BAL samples. RESULTS: MMPs and TIMPs were present in the cells of sarcoid granuloma, and were more prevalent in the parenchyma than in the bronchi. We found no correlation between MMP-9, MMP-2, TIMP-1, TIMP-2 and HRCT pattern or BAL cells. There were inverse associations between MMP-9 and FEV1 (% predicted), and also between MMP-2 and maximal expiratory flow 25-75% (L and % predicted) in patients with sarcoidosis diagnosed by transbronchial lung biopsy. There were no differences in the measured parameters between patients with and without fibrotic changes and between those with negative vs. positive lung biopsy results. CONCLUSIONS: Our study provides an indirect evidence for a potential involvement of MMPs/TIMPs in the sarcoid inflammation of the distal airways.